Genetic Screening

My friend Sasha is type A; she always has her ducks in a row. She's been married for several years now and is thinking of starting a family. She's read a slew of books on pregnancy and child-rearing. I think there's such a thing as too much information; Sasha disagrees. So I wasn't surprised when she asked what I knew about genetic screening. Not much, I said, but I promised I'd look into it.

My promise took me to Thornton Hospital in La Jolla. I spoke with genetic counselor Jason Chibuk, whose specialty is prenatal diagnosis. Sasha would have liked him. "The best time for people to come in if they're thinking of having children is preconception. That way, there's not the forced timeframe of making decisions while the pregnancy is ongoing."

Chibuk said that "the first and most important part of genetic screening is to sit down with someone trained in genetics and assess the family history. Genetics, more than any other specialty in medicine, focuses not only on the patient, but also on the family as a whole, for predicting the likelihood of disease. Then, if this history indicates that genetic testing is warranted, we're able to do tests. We do a three-generation pedigree, in which we're looking at siblings and parents, aunts and uncles, and grandparents for the individual at risk. So there's the cancer genetics realm, the pediatric and adult genetics realm, and the prenatal genetics realm."

A primary care physician makes the determination if a person's family history of cancer has some genetic background, said Chibuk. "Breast and ovarian cancers and colon cancers at a young age may arise from a genetic disposition that can be tested for. Then, other at-risk family members can be given appropriate reoccurrence risks. There are some women who may be at risk for ovarian cancer, and they may choose, once they're done with their childbearing years, to have their ovaries removed, instead of seeing whether the cancer strikes or not." When it comes to pediatric genetic diseases, "generally, once an affected individual comes to light, we can begin to look at the individual, look at his family history, and start analyzing. 'How did this happen?' That way, they can determine care for the individual and recurrence risks for the other family members."

In prenatal diagnosis, "there are many different types of screenings, including those done based on family history, ethnic background, blood testing, or ultrasound findings." He zeroed in on ethnic background. "Different ethnic backgrounds have elevated risks to be carriers for different genetic diseases. One in 25 Caucasians is a carrier for cystic fibrosis, a chronic lung disorder. In the African-American population, one in 10 persons is a carrier for sickle cell disease. It doesn't harm you to be a carrier, so in most circumstances you wouldn't know it if you were. But if both Mom and Dad are carriers, then the baby is at risk; there's a one-in-four chance that the baby will have the disease. There's a one-in-two chance that the baby will be a carrier. And there's a one-in-four chance that the baby is neither affected nor a carrier."

Testing is done through blood work; the nature of the test depends on what you're looking for. Chibuk took cystic fibrosis as an example. "In this case, you're looking at the CFTR gene and analyzing it for 30 of the most common mutations. A mutation is a sequence alteration within a gene that leads to the gene being unable to produce a functional gene product, or protein. The human genome is like 46 textbooks -- the chromosomes -- of genetic information. Each chromosome contains several chapters -- several genes. We read through a chapter, or a certain sentence in that chapter, where we know that spelling errors -- mutations -- are common. In the case of cystic fibrosis, there are 30 spelling errors that make up 90 percent of all the known mutations of the gene responsible and which lead to the disease." If both parents are carriers, "we might get into tests in utero, doing fetal diagnosis through a biopsy of the placenta, or through amniocentesis." (Of course, there's still the remaining 10 percent, which means that you could still be a carrier -- but it's far less likely. Added Chibuk, "With a negative test result for cystic fibrosis in a Caucasian, the risk of being a carrier is reduced from 1-in-25 to 1-in-240.")

"We offer cystic fibrosis carrier screening to all pregnant couples, or couples planning pregnancy," continued Chibuk. If ethnic background indicates the need for testing, he supposes that it will be covered by insurance. "A cystic fibrosis screening at UCSD is $150; a screening for sickle-cell disease is around $50. But those don't screen for everything. In a prenatal diagnosis, once you start doing ultrasound and amniocentesis, and then looking at the chromosomes and screening for things like Down syndrome, you're looking at a bill over $1000 [without insurance]."

After the screening, Chibuk's job is to relay the information to the patients and to act as a support if the information turns out to be stressful. "Defining the severity of a genetic disease is a difficult thing," he noted. "Cystic fibrosis is not a life-threatening condition. There is no mental retardation, and there are no clinical physical changes. In contrast, Trisomy 18 is a condition in which the baby has three copies of chromosome 18 -- we're supposed to have two. The life span of a baby with Trisomy 18 is not expected to exceed a year." Based on the information, some people may choose to abort ("which is a legal option in San Diego County through the 23rd week"), some give up their babies for special-needs adoption. "Some people just want to be prepared, to learn about the condition so they can be ready for it when the child arrives," continued Chibuk, and pregnancy is when he'd most like to see a couple.